Ask HN: What's an interesting DIY genetic engineering project?

64 points by pengwing ↗ HN
Given some hundreds of dollars and breaking no federal laws, what kind of gene editing can a software dev get done in their kitchen?

Glowing single cell organisms? Color changing Fungi? Flowers with any #rrggbb as petal color? albino lizards? Jurassic Park?

Serious question. Looking for a project that teaches me something and has a tangible result.

35 comments

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Check out the Thought Emporium [0] on YouTube, they've got a number of biology experiments that you might find interesting. My personal favorite is the one where they make a meat berry.

[0] https://www.youtube.com/channel/UCV5vCi3jPJdURZwAOO_FNfQ

Same channel: guy engineers himself to regain lactose tolerance.
Serious? Can you link and/or summarize?
These are great and provoked me to really look into how it worked when I discovered them a few months ago.

I'd suggest watching the 2nd (retrospective) video first, and then the first video if you're interested in more detail.

Thanks to others for linking.

Summary: Guy is lactose intolerant. He inserts a sequence providing lactose tolerance into an adeno-associated virus. He then infects himself with this virus, which inserts the target sequence into his own genome.

He is then able to gorge himself on pizza without digestive problems, and he's still able to do so several months later.

The adeno-associated virus is like a retrovirus, except that, per [0], the AAV will insert at a particular location in the genome, instead of at random locations.

[0] https://www.wikiwand.com/en/Adeno-associated_virus

You could selectively breed some plant or insect with a short lifecycle, not sure what else without really expensive lab equipment.
Easy: having children.
Way over budget!
OK, then how about inviting friends with kids into your kitchen and study their similarities...
I did that. In the kitchen, actually.
Correct, though that's a very long-term experiment with a low sample size. I was going to suggest the bar scene.
Currently in phase 2, daycare is like having a 2nd mortgage. Plus, I'm exhausted all the time.
I can't agree more, 6 kids, (5 under 7), and my wife had to give up a low 6 figure job as it didn't make financial sense to pay childcare. Things will get better...
Won't fit within the stated budget and too risky. Better to stick with something safer like bombarding yourself with gamma rays.
Why don't you experiment with coming up with a new 'cultivar' or 'variety' by growing some 'dioecious' plants or trees?

For example, apples are cultivars because if you grow an apple seed from a delicious apple you eat, the apples that get produced from your tree won't taste anything like the original. Orchards get around issue with growing tasty apples you love to eat by taking 'cuttings' (which are in essence a clone copy of that tree) from the parent tree and growing the cuttings into full mature trees.

Now I'm not saying grow apples, but look at interesting plants/trees that interest you and what you want to accomplish. Do you want to improve make a fruit more tasty? Faster growing plant? More medically potent effect? Etc.

> In short, a cultivar is a plant that is produced and maintained by horticulturists but does not produce true-to-seed; whereas, a variety is a group of plants within a species that has one or more distinguishing characteristics and usually produces true-to-seed. [0]

[0] - https://extension.unl.edu/statewide/buffalo/Yard/Cultivar%20...

The classic basic first exercise with genetic engineering is to make creatures glow in the dark. Lots of news has been made by doing this to animals, but one rather safe and low impact variation is to make glow in the dark yeast and then use that to make glow in the dark beer. Do some searching for "add gene glow in the dark" or some similar and you should find plenty of material. There was at least one open science outfit that was trying to make a basic tutorial for this process.
You mean add fluorescence, not glow in the dark, right? It's not trivial to generate the necessary luciferin/luciferase, but adding GFP is a basic project.
Yes, but somehow the term "glow in the dark" ends up getting used for this even in some of the more scientific coverage so it may be useful as a search term.
I have experience in DIY genetic engineering (have run a DIY home genetic engineering lab for almost 10 years now https://www.nytimes.com/2018/05/14/science/biohackers-gene-e... )

What you can do and what you can do are different things. Genetic engineering and biological manipulation go as deep as software, and tacit knowledge about execution is non-trivial to the point where you WILL mess up experiments (so expect to repeat a lot).

That said, you can still do some fun stuff. I would recommend trying to do something very small but actually novel. For example, if you've done a GFP transformation into E.coli, try to get the GFP transformation working in a new organism (maybe a yogurt bacteria). Keep it small though, and keep it single cellular, or else you are putting yourself into the pit of despair.

Also check out the Poly project (https://github.com/TimothyStiles/poly). We're basically building (decent) open-source software for doing synthetic biology. Since you're a software developer, doing code reviews and reading our mega-comments (like https://github.com/TimothyStiles/poly/blob/prime/transformat...) might help you understand some more of the fundamental engineering problems we synthetic biologists are encountering. Also, in code reviews, if you don't understand something, a practicing synthetic biologist will explain it to you so that we can improve our docs.

I'm really sorry- I don't mean to come across as negative, but I think you're asking the wrong question. You know what you want to learn about but don't know what you want to learn.

You say you're "Looking for a project that teaches me something".

You need to figure out what that something is, then then look for a minimum viable experiment to work your way toward it.

Hmm, if someone says, what’s a project to teach me about programming, there’s a ton.

It is also well-defined in its own way, you need to know something before you even know how to narrow down your interests.

A 0th step, “what’s a cool project roughly in this area” seems like a well-posed question.

Okay, I can see your point. And I'll take you up on your offer.

What's a project to teach me about programming?

Have a go at Logo - program a turtle. Make a Pythagoras tree with it, or any other fractal. Koch snowflake is also fun.

Make a game for guessing a number 0..100 - game gives you “Goldilocks feedback”.

Make a program that sorts numbers.

Make a pong game.

Make a Harry Potter “sorting hat”: ask a few questions and allocate to one of the houses on some silly rules.

Just off the top of my mind.

Dunno how sterile "gene editing" techniques need to be, but doing kitchen lab work that's sterile enough to grow only the fungi you want is possible. I think the difference between real labs and kitchen work becomes a matter of error tolerance, prepare for failures and you can reach "good enough."

Tormenting small things with short life cycles in hopes of finding interesting adaptations and mutations is certainly doable in a kitchen, or in a closet fermenting tank and drink some of the byproducts. Its an interesting argument was a new sourdough culture or brewers yeast "developed" or "domesticated" or just "caught".

I'll plug these guys - took their 101 and 102 courses online a while back. I agree with koeng's comment that what you can do and what you can do are different - lab technique is a steeper learning curve than concepts for those of us who didn't do science degrees - but it's fascinating all the same and the closest thing I know to guided experiments.

https://www.the-odin.com/all-products/

Optogenetic experiments with C. Elegans can be done at home. You can pick up cheap high-powered LEDs from online retailers. I think plasmid and viral vectors are within your price range of a few hundred dollars for the popular Chr2 strains. Here's a lab write-up from Caltech's freshman bio class:

http://bi1x.caltech.edu/2019/handouts/c_elegans_optogenetics...

It skips the process of getting your worms to express Chr2, but there's protocols to help with that:

https://journals.plos.org/plosone/article?id=10.1371/journal...

Its not wet lab work, but there is ENORMOUS amounts of biological/genomic data at places like the Protein Data Bank [1] and through the NIH[2] (among countless others). Building something like a genome annotator or cross-species DNA/RNA/Protein comparator might not be the most sexy but you'll need some familiarity with these types of tools if you want to do any (successful) gene editing.

Towards wet lab, a lot of the actual reagents (DNA oligos, enzymes, etc.) are not going to be easy to get for personal use (for obvious reasons), but an understanding of how these work is going to be necessary. You'll need to know how to use PCR but you won't be able to get an instrument for under a few hundred dollars on eBay, so you could program/build your own thermocycler (for example using a spare CPU[3]).

If you want to participate in these types of experiments without getting your hands wet, you can also check out the online games Eterna[4] (for RNA design, out of Stanford) or FoldIT[5] (for protein design, out of UWash). I used to be involved in the lab that runs Eterna and some of the stuff they're working on is very cool - mRNA vaccines, artificial ribosomes, and fluorescent molecular sensors.

[1] - https://www.rcsb.org/ [2] - https://www.ncbi.nlm.nih.gov/genome/ [3] - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165218/ [4] - https://eternagame.org/ [5] - https://fold.it/

SARS-CoV-2 Spike Protein as a vaccine. Yes, people already did this and published recipes.
Grow some various peas. Carefully and in a controlled manner cross pollinate them. Follow traits like wrinkled peas vs smooth peas, or yellow peas vs green peas. If keep good records and do a bit of math, you'll learn a lot about genetics, and also have a bunch of fresh peas.you can eat this experiment.
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